Alternatives to the Cerebrospinal Fluid Venereal Disease Research Laboratory Test for Neurosyphilis Diagnosis

Background: The diagnosis of neurosyphilis relies in large part on the cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test, which is diagnostically specific but not sensitive. Methods: We determined the sensitivity and specificity of 3 CSF tests in addition to the CSF-VDRL in participants with syphilis enrolled in a research study: detection of Treponema pallidum ribosomal RNA, T. pallidum particle agglutination titer, and chemokine (C-X-C motif) ligand 13 (CXCL13) concentration. Neurosyphilis was defined as asymptomatic or symptomatic meningitis: CSF white blood cells >10/mu L without or with neurological symptoms, including new vision or hearing loss. Results: Cerebrospinal fluid-VDRL, CSF T. pallidum ribosomal RNA detection, and CSF T. pallidum particle agglutination titer >= 1:640 were specific (89%-96%) but not sensitive (12%-48%). In contrast, diagnostic sensitivity of CSF-CXCL13 thresholds established from receiver operating characteristic curves using the Youden index was 78% to 83% and specificity was 76% to 81%. In individuals with nonreactive CSF-VDRL, neurosyphilis diagnosis could be confirmed by CSF-CXCL13 concentration in 69% to 75%. Conclusions: Further studies of CSF-CXCL13 should include CSF samples from multiple cohorts and countries and should use standard neurosyphilis definitions to establish uniform thresholds for diagnosis.